Neurofibromatosis

Epidemiology

  • Two Types of Neurofibromatosis
    • Neurofibromatosis 1 (von Recklinghausen’s Disease): autosomal dominant inheritance
      • Mutation in NF1 gene at 17q11
    • Neurofibromatosis 2

Physiology

  • Fibrotic neurofibromas of lung

Pathologic Patterns

  • Interstitial Lung Disease: usual interstitial pneumonia (UIP) features may be seen in some cases
  • Pulmonary Hypertension
    • May be related to pulmonary fibrosis and/or chronic thromboembolic pulmonary HTN
    • In rare cases, pulmonary arteries and veins manifest intimal hypertrophy and fibrosis
  • Systemic Vasculopathy: occasionally complicates the disease
  • Neurofibromatosis type 1 gene modulates protein kinase B (a regulator of cell proliferation)

Diagnosis

  • CXR/Chest CT Patterns
    • ILD: upper lobe-predominance
      • Bullous changes eventually appear in upper lung zones
      • Hyperinflation: later
    • Lung nodules: due to metasases from neural tumor (may occur apically producing a Pancoast-like tumor) or due to benign neurofibromas
      • Benign Neurofibroma: solitary lung nodule (usually well-defined)/Location: no lobar predilection/Calcification: rare/Cavitation: none
    • Rib Notching (inferior): due to intercostal neurofibroma
    • Mediastinal mass: due to mediastinal vagal nerve neurofibroma/ meningocele
    • Kyphoscoliosis:
    • Pneumothorax:
  • OLB: cellular and fibrotic interstitial pneumonia

Clinical Manifestations

Dermatologic Manifestations

  • Cafe-Au-Lait Spots
  • Subcutaneous Neurofibromas: may involve chest wall and intercostal space

Ophthalomologic Manifestations

  • Lisch Nodule in Iris

Pulmonary Manifestations

Apical Neurofibroma (Pancoast Syndrome)

  • xxx

Intercostal Neurofibromas

  • Diagnosis
    • Chest X-Ray (see Chest X-Ray, [[Chest X-Ray]]): inferior rib notching

Interstitial Lung Disease (ILD) (see Interstitial Lung Disease, [[Interstitial Lung Disease]]): occurs in 10-25% of cases

  • Epidemiology: interstitial lung disease is the most common lung manifestation in neurofibromatosis
  • Diagnosis
    • Pulmonary Function Tests (PFT’s) (see Pulmonary Function Tests, [[Pulmonary Function Tests]]): restrictive early, obstructive later (due to later involvement of small airways)
    • Chest CT (see Chest Computed Tomography, [[Chest Computed Tomography]]): lower zone-predominant interstitial infiltrates, eventual appearance of bullous upper zone disease
  • Clinical
    • Dyspnea (see Dyspnea, [[Dyspnea]]): first appears between 20’s-50’s

Lung Nodule (see Lung Nodule or Mass, [[Lung Nodule or Mass]])

  • Usually asymptomatic

Mediastinal Meningocele (see xxxx, [[xxxx]])

  • xx

Mediastinal Vagus Nerve Neurofibroma (see xxxx, [[xxxx]])

  • xxx

Neural Tumor Mets to Lung (see xxxx, [[xxxx]])

  • May occur in apices (producing Pancoast syndrome)

Pneumothorax (see Pneumothorax, [[Pneumothorax]])

  • Epidemiology
  • Physiology

Pulmonary Hypertension (see Pulmonary Hypertension, [[Pulmonary Hypertension]])

  • Epidemiology
  • Clinical

Scar Carcinoma (see Lung Cancer, [[Lung Cancer]])

  • Epidemiology: has been reported

Renal Manifestations

Hypertension (see Hypertension, [[Hypertension]])

  • xxx

Rheumatologic Manifestations

Atlantoaxial Instability (see Atlantoaxial Instability, [[Atlantoaxial Instability]])

  • xxx

References

  • Type 1 neurofibromatosis complicated by pulmonary artery hypertension: a case report. J Med Invest 2007;54:354–8
  • Pulmonary hypertension in neurofibromatosis. Am J Cardiol 2007;99:1177-8
  • von Recklinghausen disease complicated by pulmonary hypertension. Chest 2001;119:1606-8
  • Pulmonary hypertension secondary to neurofibromatosis: intimal fibrosis versus thromboembolism. Thorax 1999;54:858-9.
  • Is pulmonary arterial hypertension in neurofibromatosis type 1 secondary to a plexogenic arteriopathy? Chest 2007;132:798-808